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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study of the pathogenesis of bovine ephemeral fever confirmed that the major clinical signs were fever lasting no more than 2 days, with increased respiratory rate, dyspnoea and some degree of lameness. Haematological observations revealed a neutrophilia with a left shift and a lymphopaenia at the time of peak clinical reaction. The net result was a slight leucopaenia on the day after this reaction. The most prominent pathological changes involved the lungs and synovial joints. Pulmonary emphysema and alveolar collapse with bronchiolitis, degenerative changes in synovial membranes and increased synovial fluid were observed. Specific fluorescence indicating the presence of BEF viral antigen could be detected at the time of peak clinical response in individual cells in the lungs, spleen and lymph nodes as well as neutrophils. Before and after the peak fever some fluorescence was seen in cells which appeared to be reticular cells in the lymph nodes. Viral isolation in mice could be made from blood, lungs, spleen and lymph nodes over a period of no more than 3 days. It is postulated that viral growth takes place mainly in the reticuloendothelial cells in the lungs, spleen and lymph nodes and not in vascular endothelium or lymphoid cells.
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PMID:Studies on the pathogenesis of bovine ephemeral fever. 33 60

The lung contains a host of extracellular matrix components that comprise the supporting and adhesive elements of conducting airways, alveoli and the vascular tree. While none of these components is unique to the lung, their peculiar distribution determines the architecture and function of this gas exchange organ. Cells and tissues of the lung interact with the matrix through a variety of surface receptors, especially the integrins and adhesive molecules, some of which may play important roles in lung injury and repair. Collagen type I is the predominant determinant of tensile strength, but as many as 11 other genetic types of collagen with specialized adhesive and connecting functions can be found in various lung structures, including cartilage and basement membranes. Excessive matrix accumulation in the lung is the result of a complex set of influences on gene regulation, part of which may be due to the presence of inflammatory cytokines that directly stimulate matrix synthesis. However, degradation and turnover of the matrix are also critical processes influenced by many of the same mediators. Collagenase and gelatinase (type IV collagenase) are tightly-regulated metalloenzymes that, together with a set of specific inhibitors of metalloproteinases, determine the net abundance and distribution of collagen. Elastases of several biochemical types are also under tight regulation by proteinase inhibitors. Elastin is essential to lung function at the level of alveolar wall resiliency and patency, and loss of elastin in emphysema appears to be due to uncontrolled degradation of the embryologically-established pattern of elastic fibres accompanied by nonfunctional replacement as a response to injury. Injury to the vascular endothelium of the lung, as well as other physiological insults that elevate pulmonary blood pressure, can lead to the excessive accumulation of collagen and elastin in the conductance and resistance arteries of the pulmonary circulation. Mechanical stress and endothelial injury may mediate the medial hypertrophy of these vessels. Extracellular matrix components are critically involved in every stage of lung biology: development, normal function and acute and chronic disease states. To date, only glucocorticoids, cross-linking inhibitors, and protease inhibitors have been used in a general attempt to suppress either excessive matrix accumulation or loss. More detailed understanding of the regulation and specific interactions of matrix components is central to the analysis of disease states and the development of appropriate therapeutic strategies.
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PMID:Biochemistry and turnover of lung interstitium. 228 53

We report a case of aneurysm of the abdominal aorta with spontaneous rupture in a 64-year-old man with emphysema and chronic alcoholism. Campylobacter fetus subspecies fetus was repeatedly recovered from the blood and from specimens of the excised aneurysm. The patient died in spite of early diagnosis, intravenous erythromycin and surgical intervention. The bacteriology and epidemiology of campylobacteriosis in man is briefly discussed and eight other published cases of aneurysm, infected with the same organism, are tabulated. C. fetus ssp. fetus should be added to the list of bacteria having a tropism for vascular endothelium.
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PMID:Campylobacter fetus subspecies fetus infection of an abdominal aneurysm. 267 60

Under normal conditions, there is a sizeable pool of marginated granulocytes in the lung circulation which is in dynamic equilibrium with the circulating granulocyte pool. The number of granulocytes in the lungs' microcirculation may depend on pulmonary blood flow or biochemical interactions between granulocytes and pulmonary vascular endothelium, or both. There is some evidence that normal lung function may be affected by granulocytes. Several acute and chronic diseases may result, at least in part, from interactions of granulocytes with the lungs. Acute diffuse lung injury (adult respiratory distress syndrome) is characterized by diffuse pulmonary inflammation, and, in animal models, some of the lung dysfunction depends on the presence of granulocytes. Bronchoconstriction and airway hyperreactivity, characteristic of asthma, may be influenced by granulocyte-generated products of arachidonic acid. Granulocyte-derived proteases and oxidants may contribute to the pathogenesis of pulmonary emphysema and may affect connective tissue synthesis in interstitial pulmonary fibrosis. There is some evidence suggesting a connection between granulocytes and chronic pulmonary hypertension. The fact that some interventions which cause pulmonary leukostasis do not cause severe, persistent lung injury indicates that as yet unknown factors may determine whether interactions of granulocytes with the lungs are benign or pathological. Such factors could include the generation of humoral substances, and metabolites of arachidonic acid are particularly interesting in this regard. Research related to interactions of granulocytes with the lungs suggests strongly that such interactions are integral to the pathogenesis of several lung diseases. Understanding those diseases will require further basic studies of granulocyte behavior and the modes of communication between cells intrinsic to the lung and granulocytes.
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PMID:Interactions of granulocytes with the lungs. 637 88

New Zealand rabbits were exposed in inhalation chambers to 3,000 ppm of n-hexane 8h/d for 8 d, and the acute respiratory effects were studied by light and electron microscopy. Animals intoxicated showed morphological changes in the lung parenchyma characterized by centriacinar emphysema and scattered micro haemorrhages. Lung damage was most severe at the transition zone from terminal bronchiole to alveolar ducts. This centriacinar lesion consisted to degenerative and necrotic phenomena in bronchiolar epithelium with cellular desquamation, increased number of macrophages within proximal alveoli of alveolar ducts, increased number and size of lamellar bodies in alveolar type II cells, changes in the vascular endothelium. Focal subpleural atelectasis, alveolar and interstitial oedema were also found. The segmental distribution of the pulmonary lesions were confirmed by transmission electron microscopy.
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PMID:Respiratory tract lesions induced in rabbits by short-term exposure to N-hexane. 740 71

The common fatal hereditary disorders, alpha 1-antitrypsin (alpha 1AT) deficiency and cystic fibrosis (CF), are clinical models for the common lung diseases, emphysema and chronic bronchitis, respectively. Both are potentially amenable to therapeutic intervention by gene therapy, in which the relevant gene is used to modify cells of the affected individual. Although the gene therapy strategies for these diseases are conceptually quite different, a promising approach for both is the in vivo administration of a recombinant replication deficient adenovirus vector containing a normal copy of the abnormal gene. If the goal is to express the normal extracellular anti-protease alpha 1 AT, the route of administration could be directly into the lung, liver or vascular endothelium. If the goal is to express the normal transmembrane protein defective in CF epithelial cells, the new gene will need to be delivered directly to the affected cells. The feasibility of these approaches has been demonstrated in vitro and in vivo in experimental animals.
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PMID:Gene therapy for pulmonary diseases. 829 Mar 11

Because more than 90 percent of [123I]hydroxyiodobenzyl-propanediamine (HIPDM) is localized in the lung after intravenous injection, the radiopharmaceutical has been proposed as a lung imaging agent. Its potential usefulness for the detection of pulmonary emphysema was evaluated in an animal model of elastase-induced emphysema along with [99mTc]MAA lung perfusion imaging. To induce lung emphysema, Long-Evans rats (200-250 g) were given 400 IU/Kg elastase intratracheally under ether anesthesia. Four weeks after elastase treatment, 15 treated and 15 nontreated rats were paired and simultaneously imaged under a scintillation camera immediately following intravenous injection of 0.25-0.3 mCi[99mTc]MAA. The procedure was repeated 48 hr later using 0.25-0.3 mCi[123I]HIPDM. Activity in the region of interest (ROI) over the lungs was recorded after the injections. Total counts per ROI from each rat were measured and normalized by lung volume. The normalized lung activity ratio of treated/nontreated rats was computed. The mean ratios of HIPDM and MAA were 0.847 and 0.802, respectively. The significant decrease in uptake of both HIPDM (p < 0.021) and of MAA (p < 0.025) in the elastase-treated lungs indicates decrease in functioning vascular endothelium and decrease in number of pulmonary capillary vessels, respectively, reflecting damage in capillaries and small arterioles. The decrease in treated/nontreated ratios lung is consistent with a significant alteration in pulmonary function and a significant increase in mean linear intercept (p < 0.005) in treated lung. Since the imaging reflects pulmonary endothelial receptor function, [123I]HIPDM lung imaging may serve as an alternative diagnostic modality for pulmonary emphysema.
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PMID:[123I]HIPDM pulmonary imaging demonstrates elastase-induced pulmonary emphysema. 841 18

The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.
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PMID:Expression of Egr-1 in late stage emphysema. 1102 35

Targeted disruption of the klotho gene induces multiple phenotypes characteristic of human aging, including arteriosclerosis, pulmonary emphysema and osteoporosis. Moreover, we previously observed that insufficient klotho expression in mice leads to endothelial dysfunction. In the present study, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which exhibit hypertension, obesity, severe hyperglycemia and hypertriglyceridemia, and are thus considered an animal model of atherogenic disease, to test the effects of oral administration of troglitazone (200 mg/kg) on renal klotho mRNA expression and endothelial function. Systolic blood pressure, body weight, plasma glucose and triglyceride levels were all significantly higher in 30-week-old OLETF rats than in controls (LETO; Long-Evans Tokushima Otsuka) (p<0.05, n=7). In addition, endothelium-dependent relaxation of the aorta in response to 10(-5) M acetylcholine was significantly attenuated in OLETF rats (p<0.05, n=7), as was renal expression of klotho mRNA. Administration of troglitazone for 10 weeks significantly reduced systolic blood pressure, plasma glucose and triglyceride levels in OLETF rats, while augmenting endothelium-dependent aortic relaxation and renal klotho mRNA expression. These findings suggest that troglitazone protects the vascular endothelium against damage caused by the presence of multiple atherogenic factors.
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PMID:Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors. 1176 31

Delivery of genes to the pulmonary vascular endothelium is a rational approach for the investigation and potential therapy of pulmonary vascular diseases. Furthermore, in view of the exposure of this vascular bed to the entire cardiac output, this technique could be used as an efficient basis to achieve systemic delivery of secreted factors. The attraction of direct gene delivery to endothelium for the therapy of vascular disease has been especially heightened in the last couple of years in view of the new discoveries concerning the genetic basis of primary pulmonary hypertension (PPH). In brief, mutations in the bone morphogenetic protein receptor type 2 (BMPR2, a member of the transforming growth factor-beta [TGF-beta] family of receptors) gene have been found in many patients with familial PPH. Subsequent in vitro studies have confirmed an association between BMPR2 mutations and abnormal proliferative responses in pulmonary endothelial and smooth-muscle cells (2). Other TGF-beta signaling pathways may also be involved in this process, and the mechanisms involved may also have relevance for the more common cases of pulmonary vascular disease secondarily associated with chronic airways obstruction, connective tissue diseases, and perhaps HIV infection. Additionally, new evidence is emerging concerning the role of the vasculature in the pathogenesis of emphysema.
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PMID:Delivery of DNA to pulmonary endothelium using adenoviral vectors. 1497 May 86


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